tbuckley/cabot-search huggingface dataset:
Sustained delivery approaches to improving adaptive immune responses
Authors: Ben S. Ou, Olivia M. Saouaf, Julie Baillet, Eric A. Appel
Journal: Advanced Drug Delivery Reviews (2022)

The immune system is one of the most important, complex biological networks regulating and protecting human health. Its precise modulation can prevent deadly infections and fight cancer. Accordingly, prophylactic vaccines and cancer immunotherapies are some of the most powerful technologies to protect against potential dangers through training of the immune system. Upon immunization, activation and maturation of B and T cells of the adaptive immune system are necessary for development of proper humoral and cellular protection. Yet, the exquisite organization of the immune system requires spatiotemporal control over the exposure of immunomodulatory signals. For example, while the human immune system has evolved to develop immunity to natural pathogenic infections that often last for weeks, current prophylactic vaccination technologies only expose the immune system to immunomodulatory signals for hours to days. It has become clear that leveraging sustained release technologies to prolong immunogen and adjuvant exposure can increase the potency, durability, and quality of adaptive immune responses. Over the past several years, tremendous breakthroughs have been made in the design of novel biomaterials such as nanoparticles, microparticles, hydrogels, and microneedles that can precisely control the presentation of immunomodulatory signals to the immune system. In this review, we discuss relevant sustained release strategies and their corresponding benefits to cellular and humoral responses.
New Test to Help Diagnose Alzheimer Disease
Authors: Rita Rubin
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prevalence of Cardiovascular Disease in Patients With Potentially Curable Malignancies
Authors: Nicolò Matteo Luca Battisti, Catherine A. Welch, Michael Sweeting, Mark de Belder, John Deanfield, Clive Weston, Michael D. Peake, David Adlam, Alistair Ring
Journal: JACC CardioOncology (2022)

Although a common challenge for patients and clinicians, there is little population-level evidence on the prevalence of cardiovascular disease (CVD) in individuals diagnosed with potentially curable cancer.We investigated CVD rates in patients with common potentially curable malignancies and evaluated the associations between patient and disease characteristics and CVD prevalence.The study included cancer registry patients diagnosed in England with stage I to III breast cancer, stage I to III colon or rectal cancer, stage I to III prostate cancer, stage I to IIIA non-small-cell lung cancer, stage I to IV diffuse large B-cell lymphoma, and stage I to IV Hodgkin lymphoma from 2013 to 2018. Linked hospital records and national CVD databases were used to identify CVD. The rates of CVD were investigated according to tumor type, and associations between patient and disease characteristics and CVD prevalence were determined.Among the 634,240 patients included, 102,834 (16.2%) had prior CVD. Men, older patients, and those living in deprived areas had higher CVD rates. Prevalence was highest for non-small-cell lung cancer (36.1%) and lowest for breast cancer (7.7%). After adjustment for age, sex, the income domain of the Index of Multiple Deprivation, and Charlson comorbidity index, CVD remained higher in other tumor types compared to breast cancer patients.There is a significant overlap between cancer and CVD burden. It is essential to consider CVD when evaluating national and international treatment patterns and cancer outcomes.
Looking Upstream–The Role of Primary Care in Addressing US Race Inequities in Kidney Health
Authors: L. Ebony Boulware
Journal: Journal of the American Society of Nephrology (2022)

Early evidence of racial inequities in kidney health frequently emerges in primary care settings. Despite this, the vast majority of attention to racial inequities in kidney health has been paid toward identifying and addressing inequities in late stages of kidney disease and specialty care,
L-5-hydroxytryptophan promotes antitumor immunity by inhibiting PD-L1 inducible expression
Authors: Jing Huang, Xiaobo Wang, Bing Li, Shiyu Shen, Ruina Wang, Hongru Tao, Junchi Hu, Jin Yu, Hualiang Jiang, Kaixian Chen, Cheng Luo, Yongjun Dang, Yuanyuan Zhang
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background The repression or downregulation of programmed death-ligand 1 (PD-L1) can release its inhibition of T cells and activate antitumor immune responses. Although PD-1 and PD-L1 antibodies are promising treatments for diverse tumor types, their inherent disadvantages and immune-related adverse events remain significant issues. The development of small molecule inhibitors targeting the interaction surface of PD-1 and PD-L1 has been reviving, yet many challenges remain. To address these issues, we aimed to find small molecules with durable efficacy and favorable biosafety that alter PD-L1 surface expression and can be developed into a promising alternative and complementary therapy for existing anti-PD-1/PD-L1 therapies. Methods Cell-based screen of 200 metabolic molecules using a high-throughput flow cytometry assay of PD-L1 surface expression was conducted, and L-5-hydroxytryptophan (L-5-HTP) was found to suppress PD-L1 expression induced by interferon gamma (IFN-γ). Inhibition of PD-L1 induction and antitumor effect of L-5-HTP were evaluated in two syngeneic mouse tumor models. Flow cytometry was performed to investigate the change in the tumor microenvironment caused by L-5-HTP treatment. Results We discovered that L-5-HTP suppressed IFN-γ-induced PD-L1 expression in tumor cells transcriptionally, and this effect was directly due to itself. Mechanistically, L-5-HTP inhibited IFN-γ-induced expression of RTK ligands and thus suppressed phosphorylation-mediated activation of RTK receptors and the downstream MEK/ERK/c-JUN signaling cascade, leading to decreased PD-L1 induction. In syngeneic mouse tumor models, treatment with 100 mg/kg L-5-HTP (intraperitoneal) inhibited PD-L1 expression and exhibited antitumor effect. L-5-HTP upregulated the ratio of granzyme B+ CD8+ activated cytotoxic T cells. An intact immune system and PD-L1 expression was critical for L-5-HTP to exert its antitumor effects. Furthermore, L-5-HTP acted synergistically with PD-1 antibody to improve anticancer effect. Conclusion Our study illustrated L-5-HTP’s inhibitory effect on PD-L1 induction stimulated by IFN-γ in tumor cells and also provided insight into repurposing L-5-HTP for use in tumor immunotherapy.
Cardiopulmonary Consequences of Vaping in Adolescents: A Scientific Statement From the American Heart Association
Authors: Loren E. Wold, Robert Tarran, Laura E. Crotty Alexander, Naomi M. Hamburg, Farrah Kheradmand, Gideon St. Helen, Joseph C. Wu
Journal: Circulation Research (2022)

Although the US Food and Drug Administration has not approved e-cigarettes as a cessation aid, industry has at times positioned their products in that way for adults trying to quit traditional cigarettes; however, their novelty and customizability have driven them into the hands of unintended users, particularly adolescents. Most new users of e-cigarette products have never smoked traditional cigarettes; therefore, understanding the respiratory and cardiovascular consequences of e-cigarette use has become of increasing interest to the research community. Most studies have been performed on adult e-cigarette users, but the majority of these study participants are either former traditional smokers or smokers who have used e-cigarettes to switch from traditional smoking. Therefore, the respiratory and cardiovascular consequences in this population are not attributable to e-cigarette use alone. Preclinical studies have been used to study the effects of naive e-cigarette use on various organ systems; however, almost all of these studies have used adult animals, which makes translation of health effects to adolescents problematic. Given that inhalation of any foreign substance can have effects on the respiratory and cardiovascular systems, a more holistic understanding of the pathways involved in toxicity could help to guide researchers to novel therapeutic treatment strategies. The goals of this scientific statement are to provide salient background information on the cardiopulmonary consequences of e-cigarette use (vaping) in adolescents, to guide therapeutic and preventive strategies and future research directions, and to inform public policymakers on the risks, both short and long term, of vaping.
Hospitalization and Emergency Department Encounters for COVID-19 After Paxlovid Treatment — California, December 2021–May 2022
Authors: Deborah E. Malden, Vennis Hong, Bruno J. Lewin, Bradley K. Ackerson, Marc Lipsitch, Joseph A. Lewnard, Sara Y. Tartof
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Nirmatrelvir/ritonavir (Paxlovid) is a combination protease inhibitor that blocks replication of SARS-CoV-2 (the virus that causes COVID-19) and has been shown to reduce the risk for hospitalization and death among patients with mild to moderate COVID-19 who are at risk for progression to severe disease* (1). In December 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for early treatment with Paxlovid among persons with mild to moderate cases of COVID-19 who are at high risk for progression to severe disease (2). FDA and a small number of published case reports have documented recurrence of COVID-19 symptoms or a positive viral test result (COVID-19 rebound) 2-8 days after recovery or a negative SARS-CoV-2 test result among patients treated with Paxlovid (3-7); however, large-scale studies investigating severe illness after Paxlovid treatment are limited. This study used electronic health record (EHR) data from a large integrated health care system in California (Kaiser Permanente Southern California [KPSC]) to describe hospital admissions and emergency department (ED) encounters related to SARS-CoV-2 infections during the 5-15 days after pharmacy dispensation of a 5-day treatment course of Paxlovid. Among 5,287 persons aged ≥12 years who received Paxlovid during December 31, 2021-May 26, 2022, 73% had received ≥3 doses of COVID-19 vaccine†, and 8% were unvaccinated. During the 5-15 days after Paxlovid treatment was dispensed, six hospitalizations and 39 ED encounters considered to be related to SARS-CoV-2 infection were identified, representing <1% of all patients to whom Paxlovid treatment was dispensed during the study period. Among these 45 persons, 21 (47%) were aged ≥65 years, and 35 (78%) had at least one underlying medical condition§ (8). This study found that hospitalization or ED encounters for COVID-19 during the 5-15 days after Paxlovid treatment was dispensed for mild to moderate COVID-19 illness were rarely identified. When administered as an early-stage treatment, Paxlovid might prevent COVID-19-related hospitalization among persons with mild to moderate cases of COVID-19 who are at risk for progression to severe disease.
From surviving to thriving: integrating mental health care into HIV, community, and family services for adolescents living with HIV
Authors: Lucie D Cluver, Lorraine Sherr, Elona Toska, Siyanai Zhou, Claude-Ann Mellins, Olayinka Omigbodun, Xiaoming Li, Samuel Bojo, Tonya Thurman, Wole Ameyan, Chris Desmond, Nicola Willis, Christina Laurenzi, Amahle Nombewu, Mark Tomlinson, Noxolo Myeketsi
Journal: The Lancet Child & Adolescent Health (2022)
Research Quality and Impact of Cardiac Rehabilitation in Cancer Survivors
Authors: Reza Fakhraei, Serena S. Peck, Husam Abdel-Qadir, Paaladinesh Thavendiranathan, Catherine M. Sabiston, Fernando Rivera-Theurel, Paul Oh, Ani Orchanian-Cheff, Leanna Lee, Scott C. Adams
Journal: JACC CardioOncology (2022)
Multispecies Probiotic for the Prevention of Antibiotic-Associated Diarrhea in Children
Authors: Jan Łukasik, Thomas Dierikx, Isolde Besseling-van der Vaart, Tim de Meij, Hania Szajewska, Sophie R. D. van der Schoor, Malika Chegary, Catharina (Karen) J.M. Koning
Journal: JAMA Pediatrics (2022)

<h3>Importance</h3> The efficacy of multispecies probiotic formulations in the prevention of antibiotic-associated diarrhea (AAD) remains unclear. <h3>Objective</h3> To assess the effect of a multispecies probiotic on the risk of AAD in children. <h3>Design, Setting, and Participants</h3> This randomized, quadruple-blind, placebo-controlled trial was conducted from February 2018 to May 2021 in a multicenter, mixed setting (inpatients and outpatients). Patients were followed up throughout the intervention period. Eligibility criteria included age 3 months to 18 years, recruitment within 24 hours following initiation of broad-spectrum systemic antibiotics, and signed informed consent. In total, 646 eligible patients were approached and 350 patients took part in the trial. <h3>Interventions</h3> A multispecies probiotic consisting of<i>Bifidobacterium bifidum</i>W23,<i>Bifidobacterium lactis</i>W51,<i>Lactobacillus acidophilus</i>W37,<i>L acidophilus</i>W55,<i>Lacticaseibacillus paracasei </i>W20<i>, Lactiplantibacillus plantarum </i>W62<i>, Lacticaseibacillus rhamnosus </i>W71, and<i>Ligilactobacillus salivarius</i>W24, for a total dose of 10 billion colony-forming units daily, for the duration of antibiotic treatment and for 7 days after. <h3>Main Outcomes and Measures</h3> The primary outcome was AAD, defined as 3 or more loose or watery stools per day in a 24-hour period, caused either by<i>Clostridioides difficile</i>or of otherwise unexplained etiology, after testing for common diarrheal pathogens. The secondary outcomes included diarrhea regardless of the etiology, diarrhea duration, and predefined diarrhea complications. <h3>Results</h3> A total of 350 children (192 boys and 158 girls; mean [range] age, 50 [3-212] months) were randomized and 313 were included in the intention-to-treat analysis. Compared with placebo (n = 155), the probiotic (n = 158) had no effect on risk of AAD (relative risk [RR], 0.81; 95% CI, 0.49-1.33). However, children in the probiotic group had a lower risk of diarrhea regardless of the etiology (RR, 0.65; 95% CI, 0.44-0.94). No differences were observed between the groups for most of the secondary outcomes, including adverse events. <h3>Conclusions and Relevance</h3> A multispecies probiotic did not reduce the risk of AAD in children when analyzed according to the most stringent definition. However, it reduced the overall risk of diarrhea during and for 7 days after antibiotic treatment. Our study also shows that the AAD definition has a significant effect on clinical trial results and their interpretation. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03334604
Cardiometabolic Comorbidities in Cancer Survivors
Authors: Leah L. Zullig, Anthony D. Sung, Michel G. Khouri, Shelley Jazowski, Nishant P. Shah, Andrea Sitlinger, Dan V. Blalock, Colette Whitney, Robin Kikuchi, Hayden B. Bosworth, Matthew J. Crowley, Karen M. Goldstein, Igor Klem, Kevin C. Oeffinger, Susan Dent
Journal: JACC CardioOncology (2022)

There are nearly 17 million cancer survivors in the United States, including those who are currently receiving cancer therapy with curative intent and expected to be long-term survivors, as well as those with chronic cancers such as metastatic disease or chronic lymphocytic leukemia, who will receive cancer therapy for many years. Current clinical practice guidelines focus on lifestyle interventions, such as exercise and healthy eating habits, but generally do not address management strategies for clinicians or strategies to increase adherence to medications. We discuss 3 cardiometabolic comorbidities among cancer survivors and present the prevalence of comorbidities prior to a cancer diagnosis, treatment of comorbidities during cancer therapy, and management considerations of comorbidities in long-term cancer survivors or those on chronic cancer therapy. Approaches to support medication adherence and potential methods to enhance a team approach to optimize care of the individual with cancer across the continuum of disease are discussed.
FDA Approval Summary: Belzutifan for von Hippel-Lindau Disease–Associated Tumors
Authors: Jaleh Fallah, Michael H. Brave, Chana Weinstock, Gautam U. Mehta, Diana Bradford, Haley Gittleman, Erik W. Bloomquist, Rosane Charlab, Salaheldin S. Hamed, Claudia P. Miller, Sarah E. Dorff, Wiley A. Chambers, Bronwyn D. Mixter, Jeannette Dinin, William F. Pierce, Tiffany K. Ricks, Shenghui Tang, Martha Donoghue, Richard Pazdur, Laleh Amiri-Kordestani, Amna Ibrahim, Julia A. Beaver
Journal: Clinical Cancer Research (2022)

On August 13, 2021, the FDA approved belzutifan (WELIREG, Merck), a first-in-class hypoxia-inducible factor (HIF) inhibitor for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. The FDA granted approval based on the clinically meaningful effects on overall response rate (ORR) observed in patients enrolled in Study MK-6482-004. All 61 patients had VHL-associated RCC; some also had CNS hemangioblastomas and/or pNET. For VHL disease-associated RCC, ORR was 49% [95% confidence interval (CI), 36-62], median duration of response (DoR) was not reached, 56% of responders had DoR ≥12 months, and median time to response was 8 months. Twenty-four patients had measurable CNS hemangioblastomas with an ORR of 63% (95% CI, 41-81), and 12 patients had measurable pNET with an ORR of 83% (95% CI, 52-98). For these tumors, median DoR was not reached, with 73% and 50% of patients having response durations ≥12 months for CNS hemangioblastomas and pNET, respectively. The most common adverse reactions, including laboratory abnormalities, reported in ≥20% were anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea. Belzutifan can render some hormonal contraceptives ineffective and can cause embryo-fetal harm during pregnancy. This article summarizes the data and the FDA thought process supporting traditional approval of belzutifan for this indication.
Airway immune responses to COVID-19 vaccination in COPD patients and healthy subjects
Authors: Thomas Southworth, Natalie Jackson, Dave Singh
Journal: European Respiratory Journal (2022)

Chronic obstructive pulmonary disease (COPD) patients have a higher risk of developing severe illness and mortality following severe acute respiratory coronavirus 2 (SARS-COV-2) infection [1]. Vaccination protects against coronavirus disease 2019 (COVID-19) through the development of systemic and airway immune responses. Patients with COPD display altered humoral immunity, with reduced antibody responses compared to healthy controls (HC) [2, 3]. We studied SARS-COV-2 vaccine specific immune responses in COPD patients versus HC, using systemic, nasal and sputum samples.
Building a National Public Health System in the United States
Authors: Margaret A. Hamburg, Mandy Cohen, Karen DeSalvo, Julie Gerberding, Joneigh Khaldun, David Lakey, Ellen MacKenzie, Herminia Palacio, Nirav R. Shah
Journal: New England Journal of Medicine (2022)

In light of the shortcomings of the haphazard U.S. approach to public health, laid bare by the Covid pandemic, a Commonwealth Fund commission is proposing urgent, necessary, and realistic reforms.
Why Too Many Vitamins Feels Just About Right
Authors: Peter A. Ubel
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
TREM-2 plays a protective role in cholestasis by acting as a negative regulator of inflammation
Authors: Ibone Labiano, Aloña Agirre-Lizaso, Paula Olaizola, Anne Echebarria, Maider Huici-Izagirre, Irene Olaizola, Aitor Esparza-Baquer, Omar Sharif, Elizabeth Hijona, Piotr Milkiewicz, Malgorzata Milkiewicz, Francisco González-Romero, Patricia Aspichueta, Maria J. Monte, Jose J.G. Marin, Mihael Vucur, Tom Luedde, Marco Marzioni, Derek A. Mann, Luis Bujanda, Pedro M. Rodrigues, Jesus M. Banales, Maria J. Perugorria
Journal: Journal of Hepatology (2022)

Inflammation, particularly that mediated by bacterial components translocating from the gut to the liver and binding to toll-like receptors (TLRs), is central to cholestatic liver injury. The triggering receptor expressed on myeloid cells-2 (TREM-2) inhibits TLR-mediated signaling and exerts a protective role in hepatocellular injury and carcinogenesis. This study aims to evaluate the role of TREM-2 in cholestasis.